Tbet promotes NK cell bone marrow egress via CXCR6 expression

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Title: Tbet promotes NK cell bone marrow egress via CXCR6 expression
Authors: Cuff, A
Perchet, T
Dertschnig, S
Golub, R
Male, V
Item Type: Working Paper
Abstract: Tbet-deficient mice have reduced NK cells in blood and spleen, but increased NK cells in bone marrow and lymph nodes, a phenotype that is thought to be due to a defect in S1PR5-mediated migration. Here, we revisit the role of Tbet in NK cell bone marrow egress. We definitively show that the accumulation of NK cells in the bone marrow of Tbet-deficient (Tbx21 −/− ) animals occurs because of a cell-intrinsic migration defect. We identify a profile of gene expression, co-ordinated by Tbet, which affects the localisation of NK cells in the bone marrow. The most underexpressed gene in the absence of Tbet was Cxcr6, and we confirmed that CXCR6 protein was also not expressed in Tbet-deficient NK cells. Cxcr6-expressing ILC progenitors and immature NK cells accumulate in the bone marrow of CXCR6-deficient mice. This suggests that CXCR6 is among the mediators of migration, controlled by Tbet, that work together to coordinate NK cell bone marrow egress. Understanding NK cell bone marrow egress will become increasingly important as we move into an era in which NK cell immunotherapies are being developed.
Issue Date: 20-Mar-2019
URI: http://hdl.handle.net/10044/1/72990
DOI: https://doi.org/10.1101/583575
Publisher: bioRxiv
Copyright Statement: © 2019 The Author(s)
Publication Status: Published
Appears in Collections:Division of Surgery
Faculty of Medicine



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